In spite of the common use of skin grafts and skin flaps in plastic and reconstructive surgery, serious complications still arise that add considerable expense in terms of suffering and hospital care. The complete or partial necrosis that can occur in surgical flaps or grafts is due to prolonged tissue ischemia that compromises tissue blood flow. Prompt revascularization of the graft or flap by anastomoses and neovascularization is a major determinant of the success of graft/flap surgery. Exogenous angiogenesis factors are expected to enhance both of these processes. In the proposed studies, three angiogenic agents will be examined for their effects on skin flap survival: 1) adenosine, a product of ischemic metabolism, 2) a low molecular weight tumor-derived factor, and 3) a polypeptide angiogenesis factor, basic fibroblast growth factor. Test material at various dosages will be applied to pedicle skin flaps on rats using infusion, suffusion, and/or subcutaneous injections that will be administered at the time of surgery, pre-operatively and/or post- operatively. The results of these studies will be analyzed with regard to effects of flap necrosis and survivability. Selected specimens will be examine histologically for effects on flap vasculature as well as on other features of the repair process. These Phase I studies will determine the feasibility of employing angiogenic agents in augmenting skin flap survival. Favorable results in this system will have relevance for skin graft surgery as well as in the treatment of other would types.